The heart includes four natural valves that function to regulate flow direction as blood is pumped between the lungs and the various blood vessels. The mitral and tricuspid valves, which are known as the atrioventricular or intraflow valves operate to prevent backflow into the atria during ventricular contraction while permitting blood to flow therethrough during ventricular relaxation. The aortic and pulmonary valves are known as semilunar or outflow valves and are located where blood leaves the heart.
Semilunar valves consist of three membranous cup-like structures or cusps attached, at the same level, to the wall of a cylindrical aortic vessel so that the cusps press on each other when they are filled with blood, preventing backflow in diastole. The direction of blood flow is upward. On contraction of the vessel, that is during systole, the cusps are pressed against the vessel wall by the force of blood flowing past the attached edges of the cusps toward the free edges of the cusps, allowing the blood to flow freely.
Each open pocket of the semilunar valve defines a volume called the aortic sinus which is filled with blood when the valve is closed. If the leaflet is cut away from the wall of the aorta it can be spread out in the form of a flat hemicircular membrane. The hemicircle is the edge of the leaflet which is attached to the wall of the aorta while the top more or less linear edge was the free edge of the leaflet. Each end of the leaflets called a commisure. The work of A. A. H. J. Sauren (The Mechanical behavior of the Aortic Valve (PhD thesis) Eindhoven, The Netherlands: Eindhoven Technical University, 1981), which is incorporated herein by reference, has shown in whole mounts of leaflets that the supporting scaffold of the leaflet consists of collagen fibers, having fractile properties, which extend from one commisure to the other providing support for the applied load of blood. Equations which describe the fiber system of the leaflet have been derived by C. S. Perkin and D. M. McQueen (Mechanical equilibrium determines the fractile fiber architecture of aortic heart valve leaflets. Am. J. Physiol. 266, H319-H328, 1994) from their function which is to support a uniform load when the aortic valve is closed. What they find is a single parameter family of collagen fibers with fractile properties which compare closely with the whole mount fiber preparations. Their work serves as the basis for creating a digital program which a textile machine, or a sewing machine, could use to reproduce an approximation of the fiber scaffold of the valve leaflet.
Histologically the leaflet consists of three tissue layers, the fibrosa, the spongiosa and the ventricularis. The fibrosa of the leaflet faces the aortic wall, enclosing the fiber system described above; the fiber scaffold is arranged in corrugated fashion permitting radial expansion of the valve leaflet. Adjacent to the fibrosa is the spongiosa, a loosely organized connective tissue with collagen elastin, proteoglycans and mucopolysaccharides. Furthest away from the aortic wall is the ventricularis consisting of a sheet of elastin thought to provide the tensile recoil needed to maintain the corrugated shape of the fibrosa. The surfaces of the leaflets in contact with the blood are covered by a layer of endothelial cells.
Heart valves, e.g., semilunar valves, are deformed by a variety of pathological processes. In many cases the diseased or defective valve can be surgically removed and replaced with a prosthetic valve. Two main types of artificial valves exist: (1) mechanical valves made from metal or plastic material; and (2) valves made from animal tissue.
Artificial valves, whether mechanical or made from animal tissue, have serious drawbacks. For example, mechanical valves carry a significant risk of thrombus formation. Also, the stress associated with the junction between the stent or frame and the biological portion of the bioprosthetic valve appears to be involved in structural failure over time. Valves made from animal tissue are typically crosslinked with chemicals, e.g., glutaraldehyde during processing. Treatment of the animal tissue with glutaraldehyde causes calcification and/or the structural breakdown of the tissue, thus, reducing the area available as binding sites for human host cells. In addition, both mechanical valves and valves constructed from animal tissue do not have the capacity to grow, i.e., these types of valves can neither be occupied or remodeled by host cells nor can they be biologically integrated.
A need exists, therefore, for an improved prosthetic heart valve that overcomes or minimizes the above-mentioned problems.
The invention features novel biocompatible cardiovascular components, e.g., semilunar heart valves, for transplantation. The invention also features methods for constructing these novel biocompatible cardiovascular components which preserve the nativity of the biological materials used. In addition, the invention features a novel annular sewing ring for attachment of a cardiovascular component to the aortic wall of a host. The components can be used in vitro, for example, for model systems for research, or in vivo as prostheses or implants to replace diseased or defective heart valves. In either case, the valves can be seeded with cells, e.g., spongiosa cells, fibrosa cells, ventricularis cells, smooth muscle cells, and/or endothelial and mesothelial cells.
In one aspect of the invention, the cardiovascular component is a semilunar valve which includes a biodegradable polymer fiber scaffold, e.g., a biopolymer fiber scaffold, and collagen. In a preferred embodiment, the collagen is fetal porcine collagen. In another preferred embodiment, the collagen is fibrillar collagen. In yet another preferred embodiment, the biopolymer fiber scaffold is a collagen biopolymer scaffold.
In another aspect of the invention, the cardiovascular component is a semilunar valve which includes a biodegradable polymer fiber scaffold, e.g., a biopolymer fiber scaffold, and collagen wherein the biopolymer scaffold fiber is derived from an aortic porcine valve processed in the absence of a crosslinking agent, e.g., glutaraldehyde.
In yet another aspect of the invention, the cardiovascular component is a semilunar valve which includes a biodegradable fiber scaffold, e.g., a biopolymer fiber scaffold, and collagen wherein the scaffold has a structure determined by a digital program.
The invention further pertains to a method of making a semilunar heart valve, comprising the steps of: (a) assembling a mold which replicates the structure of a semilunar heart valve having between two lateral edges a hollow representing the aortic root and hollows representing a plurality of leaflets with outer and inner surfaces, the inner surfaces connecting with the hollow representing the aortic root, thus, forming the intimal surface of the aortic root; (b) covering the intimal surface of the hollow representing the aortic root, i.e., the surface of the hollow representing the aortic root which connects, with the hollow representing the valve leaflets, and the outside surface of the hollow representing the valve leaflets, i.e., the surface away from the aortic wall with a biodegradable polymer fiber scaffold; (c) filling the hollow representing the aortic root and the hollows representing the plurality of leaflets with collagen, e.g., fetal porcine collagen, fibrillar collagen e.g., liquid dense fibrillar collagen; and (d) freeze-drying the polymer fiber scaffold and the liquid dense collagen forming a tissue with two lateral edges.
The invention still further pertains to an annular sewing ring for attachment of a heart valve to the aortic wall of a host which includes a biopolymer cloth and a biopolymer rope shaped in a circle, wherein the biopolymer cloth is wrapped around and stitched to the biopolymer rope.
The invention yet further pertains to a semilunar heart valve made according to a method which includes the steps of: (a) assembling a mold which replicates the structure of a semilunar heart valve having between two lateral edges a hollow representing the aortic root and hollows representing a plurality of leaflets with outer and inner surfaces, the inner surfaces connecting with the hollow representing the aortic root; (b) covering the intimal surface of the hollow representing the aortic root and the outside surface of the hollow representing the plurality of leaflets with a biodegradable polymer fiber scaffold; (c) filling the hollow representing the aortic root and the hollows representing the plurality of leaflets with liquid dense collagen; and (d) freeze-drying the polymer fiber scaffold and the liquid dense collagen forming a tissue with two lateral edges.